Aberrant pre-mRNA splicing is a pervasive feature of cancer and an emerging therapeutic vulnerability. Recurrent mutations in core spliceosomal components, including SF3B1, SRSF2, U2AF1, and ZRSR2, are common in myeloid malignancies, while dysregulated splicing regulators and cis-acting splice-site alterations shape cancer-relevant isoform programs across solid tumors. Together with high transcriptional output, rapid proliferation, and oncogene-driven RNA-processing demand, these alterations can reduce the capacity of cancer cells to tolerate additional splicing perturbation, creating a therapeutic window for pharmacological splicing modulation. Multiple strategies are under investigation, including SF3B complex modulators, splicing kinase inhibitors, RBM39-directed molecular glues, PRMT/arginine-methylation-directed approaches, and selected splice-switching strategies. Early clinical experience indicates that pharmacodynamic modulation of splicing is achievable in patients, yet objective clinical benefit has been inconsistent. This reflects narrow therapeutic windows, incomplete concordance between peripheral-blood pharmacodynamic markers and tumor-tissue splicing perturbation, and the limited predictive value of mutation status alone. Rational combinations with apoptosis-targeted agents, oncogene-directed therapies, DNA-damaging agents, PARP inhibitors, and immunotherapies may offer a more effective route to clinical translation than maximal single-agent splicing inhibition. Continued progress will require more selective splicing-directed modalities, pharmacodynamic biomarkers that measure splicing perturbation in the relevant tumor or blood compartment, longitudinal mapping of genetic and tumor cell-state plasticity-driven resistance, and biomarker-defined combination trials to support expansion from hematologic malignancies into solid tumors.
The effectiveness of low-dose thoracic computed tomography (CT) screening for lung cancer for non-smokers or light smokers has been unclear. The results of the Hitachi cohort study performed by the conventional multivariable analysis suggested the reduction of lung cancer mortality by thoracic CT screening, but also revealed the lower all-cause mortality in the CT group, which indicated the existence of self-selection bias. Because the background of the subjects in the CT screening group and that in the X-ray screening group were very different, it is critical to adjust appropriately the confounding factors. In this brief report, we describe a re-evaluation of the results of the Hitachi Cohort Study performed by using more flexible methods, propensity score matching and inverse probability weighting.
BACKGROUND:Currently, there are no large cohort studies comparing the clinical outcomes of triplet therapy with those of androgen receptor pathway inhibitor (ARPI)-based doublet therapy for patients with metastatic castration-sensitive prostate cancer (mCSPC) representing real-world practice. Therefore, the present study aimed to compare whether triplet or doublet therapy is more effective in patients with mCSPC. METHODS:This large-scale retrospective cohort study used TriNetX electronic medical record data from August 2018 to July 2026, enrolling patients with mCSPC categorized as receiving triplet [darolutamide + docetaxel + androgen deprivation therapy (ADT)] or doublet therapy (enzalutamide or apalutamide + ADT). The primary outcome was overall survival (OS), while the secondary outcome was the proportion of patients achieving a PSA level ≤ 0.2 ng/ml. Propensity score matching (PSM) (1:1) was conducted to adjust for confounding variables between groups. RESULTS:Overall, 1841 patients met the eligibility criteria. Following PSM (n = 329), triplet therapy was associated with a statistically significant improvement in OS compared with doublet therapy (hazard ratio: 0.601; 95% confidence interval: 0.420-0.862; log-rank P = .005). The proportions of patients achieving PSA ≤0.2 ng/ml were 26.4% vs. 17.0% at 3 months (P = .003), 37.4% vs. 27.7% at 6 months (P = .008), 43.8% vs. 35.9% at 12 months (P = .038), and 50.5% vs. 40.1% at any time (P = .008) in the triplet and doublet groups, respectively. CONCLUSIONS:In this real-world analysis using the TriNetX database, triplet therapy including darolutamide significantly improved OS and PSA decline compared with ARPI-based doublet therapy.
BACKGROUND:Fibrous dysplasia (FD) is a benign bone disorder classified into monostotic (MFD) and polyostotic (PFD) forms. There is limited evidence available regarding the clinical management of FD, and no large-scale epidemiological or treatment reports have been published from Japan. Therefore, this study aimed to clarify FD epidemiology and management using data from the nationwide Bone and Soft Tissue Tumor (BSTT) Registry. METHODS:This study retrospectively analyzed patients with MFD and PFD registered in the BSTT Registry between 2008 and 2019. The data included patient demographics, tumor location, surgical treatment, and recurrence. Local control survival (LCS) was estimated using the Kaplan-Meier method and compared using a log-rank test. RESULTS:In total, 3181 FD cases were registered from 127 institutions (MFD, 2889; 90.8%; PFD, 292; 9.2%). The femur was the most frequently affected site in both groups. Intralesional curettage was the most frequently performed surgical procedure, accounted for in 66.9% of MFD cases and 60.8% of PFD cases. Local recurrence occurred in 2.6% and 4.2% of patients with MFD and PFD, respectively. The 1-year overall LCS rate was 97.4%, with no significant differences between groups. CONCLUSION:This study provides the largest dataset of FD in Japan, contributing to a better understanding of its epidemiology and surgical management. However, limitations, such as the underrepresentation of pediatric cases, incomplete data on non-surgical treatments, and deformity correction procedures, highlight the need for more comprehensive data to inform future treatment strategies.
Adjuvant nivolumab is an established postoperative treatment for high-risk urothelial carcinoma, but evidence for subsequent enfortumab vedotin plus pembrolizumab (EVP) after recurrence is limited. We retrospectively evaluated 17 patients with locally advanced or metastatic urothelial carcinoma who received EVP after recurrence following adjuvant nivolumab in a Japanese multi-institutional cohort. Among 16 response-evaluable patients, the objective response rate was 68.8% (11/16; exact 95% confidence interval [CI]: 41.3%-89.0%), including four complete responses and seven partial responses. Responses were observed across nivolumab-free interval groups. Median progression-free survival was 5.2 months (95% CI, 2.5-not estimable), and the median overall survival was not reached (95% CI, 8.4-not estimable). Grade 3 or higher adverse events occurred in three patients (17.6%), and one treatment-related death was recorded. These findings suggest clinically meaningful antitumor activity of EVP after recurrence following adjuvant nivolumab, warranting confirmation in larger comparative studies.
BACKGROUND:Programmed death-ligand 1 (PD-L1) Combined Positive Score (CPS) is a biomarker of nivolumab efficacy in advanced gastric cancer (AGC). Reported CPS ≥ 5 in AGC has been inconsistent across studies. We aimed to examine the distribution of CPS in real-world clinical practice using the Dako PD-L1 IHC 28-8 pharmDx (Dako 28-8) assay and to evaluate its clinical utility. METHODS:We retrospectively assessed CPS using Dako 28-8 in 138 patients with AGC treated at our institution between January 2022 and December 2022. RESULTS:The numbers of patients with CPS ≥ 5, 1 ≤ CPS < 5, and CPS < 1 were 65 (47.1%), 50 (36.2%), and 23 (16.7%), respectively. Among the patients evaluated for microsatellite instability (MSI) or tumor mutation burden (TMB), MSI-high was identified in 3/32 (9.4%), 2/31 (6.5%), and 1/20 (5.0%), while TMB-high was identified in 5/14 (35.7%), 4/20 (20.0%), and 2/11 (18.2%) in the CPS ≥ 5, 1 ≤ CPS < 5, and CPS < 1 groups, respectively. Nivolumab combination therapy was administered as first-line treatment in 14, 10, and 11 patients in the CPS ≥ 5, 1 ≤ CPS < 5, and CPS < 1 groups, respectively. Median Progression-free survival was 5.6 months in CPS ≥ 5, 5.9 months in 1 ≤ CPS < 5, and 6.5 months in CPS < 1. CONCLUSION:The frequency of CPS ≥5 in patients with AGC was approximately half of the total population. Because TMB-high tumors were identified in some patients with CPS < 5, further studies are needed to clarify the potential role of TMB in predicting ICI responsiveness in this population.
Purpose:To compare implant failure, revision surgery, and overall patient survival following endoprosthetic reconstruction versus osteosynthesis in patients undergoing surgery for metastatic bone disease of the proximal femur (MBDf). Methods:This population-based cohort study included all patients treated surgically for MBDf at six institutions in the Greater Copenhagen area, Denmark, between 2013 and 2019. Implant failure and revision surgery were analysed using competing risk models, with death treated as a competing event. Overall survival was estimated using Kaplan-Meier analysis. Results:A total of 281 patients were included, of whom 81 underwent osteosynthesis and 200 underwent endoprosthetic reconstruction. Implant failure was more frequent following osteosynthesis than endoprosthetic reconstruction, with cumulative incidences of 5% (CI 0.2 to 10), versus 0.5% (CI 0 to 1.5) at three months, 7% (CI 2 to 13) versus 0.5% (CI 0 to 1.5) at six months, and 7% (CI 2 to 13) versus 1% (CI 0 to 2.4) at twelve months. Revision surgery rates were comparable between the groups with cumulative incidences of 5% (95% CI 0.2-10) versus 3% (95% CI 0.6-5) at three months, 7% (95% CI 2-13) versus 4% (95% CI 1-6) at six months, and 9% (95% CI 3-15) versus 4% (95% CI 2-7) at twelve months. Overall survival was lower in patients treated with osteosynthesis compared with endoprosthetic reconstruction (p = 0.01). Conclusion:Endoprosthetic reconstruction is superior in terms of risk of implant failure compared to osteosynthesis in patients treated for MBDf, but no difference was found in overall revision risk.
Bone metastasis from hepatocellular carcinoma (HCC) is a marker of advanced disease and a potential cause of preventable functional loss. HCC skeletal lesions are commonly osteolytic and may be hypervascular, creating risks of pathological fracture, spinal instability, metastatic spinal cord compression (MSCC), neurological deficit, and loss of ambulation. This structured narrative review integrates HCC-specific clinical evidence with established orthopedic and spine oncology frameworks to identify when specialist consultation should occur before irreversible skeletal or neurological deterioration. Retrospective HCC cohorts indicate that the spine is frequently involved, that surveillance-detected metastases were associated with a lower observed frequency of fracture or paralysis than symptom-detected metastases, and that hepatic reserve was associated with outcomes after skeletal surgery. Because direct HCC-specific comparative evidence remains limited, the Spinal Instability Neoplastic Score (SINS), epidural spinal cord compression (ESCC)/Bilsky grading, the neurological, oncological, mechanical, and systemic (NOMS) framework, prognostic scores, Patchell's MSCC evidence, and Mirels score are used as communication aids rather than disease-specific operative thresholds. We propose a conceptual four-pathway triage model for neurological emergency, spinal mechanical failure, long-bone fracture risk, and pelvic or acetabular weight-bearing failure, followed by a systemic-fitness assessment incorporating liver reserve, hemostatic status, prognosis, rehabilitation potential, and patient goals. The framework is intended to accelerate multidisciplinary assessment, not to prescribe surgery.
OBJECTIVES:Spread through air spaces (STAS) is a poor prognostic pathological feature recently included as a histological factor in the ninth edition of the TNM (tumor, node, and metastasis) classification. However, its clinical significance in lung adenocarcinoma with epidermal growth factor receptor (EGFR) gene mutations remains unclear. Here, we aimed to evaluate the clinical significance of STAS according to EGFR mutation status. METHODS:We retrospectively reviewed 347 patients with completely resected pathological stage 0-IIIB lung adenocarcinoma who were evaluated for both STAS and EGFR mutations between 2015 and 2022. We investigated the association between clinicopathological features and STAS and analyzed its prognostic relevance based on EGFR mutation status. RESULTS:STAS and EGFR mutations were present in 85 (24.5%) and 178 (51.3%) patients, respectively. In patients with EGFR-mutated lung adenocarcinoma, STAS was significantly more prevalent in those with exon 19 deletions than those with the L858R mutation (P = .012). STAS was significantly markedly associated with poorer recurrence-free and overall survival in patients both with (P < .001 and P < .001, respectively) and without (P = .003 and P = .023, respectively) EGFR mutations. Multivariable analysis revealed that STAS was an independent prognostic factor for recurrence-free and overall survival in patients with EGFR mutations (P < .001 and P = .020, respectively). However, STAS was not an independent predictor in patients without EGFR mutations. CONCLUSIONS:STAS is a key pathological feature of lung adenocarcinoma and holds considerable clinical relevance, particularly in EGFR-mutated lung adenocarcinoma.
Letermovir is used for cytomegalovirus prophylaxis after allogeneic hematopoietic cell transplantation (HCT) and reportedly increases tacrolimus exposure. Isavuconazole, a mold-active triazole antifungal, also inhibits cytochrome P450 3A and may affect tacrolimus pharmacokinetics. This retrospective study evaluated tacrolimus concentration-to-dose (C/D) ratios pre- and post-conversion from continuous intravenous infusion to oral administration in allogeneic HCT recipients receiving isavuconazole. Forty-five patients were stratified according to letermovir coadministration into the isavuconazole-alone group (ISCZ-alone; n = 9) and the isavuconazole with letermovir group (ISCZ + LMV; n = 36). The median C/Dciv ratios were 17.00 and 16.40 (ng/ml)/(mg/day), respectively (P = 0.81); the median C/Dpo ratios were 3.25 and 2.60 (ng/ml)/(mg/day), respectively (P = 0.77); and the median (C/Dpo)/(C/Dciv) ratios were 0.154 and 0.173, respectively (P = 0.72). Sensitivity analyses yielded consistent findings. Letermovir coadministration was not associated with significant differences in tacrolimus C/D ratios pre- or post-conversion to oral administration in allogeneic HCT recipients receiving isavuconazole.
Background Patients with metastatic bone disease affecting the femur are at substantial risk of pathologic fracture, resulting in significant morbidity and frequently necessitating urgent surgical intervention. Accurate identification of lesions at imminent risk of fracture enables timely prophylactic fixation and improved patient outcomes. Although the Mirels score remains widely used, its limited specificity has prompted interest in CT-derived biomechanical approaches, including CT-based Structural Rigidity Analysis (CTRA) and Finite Element Analysis (FEA). Whole-femur CT is routinely obtained in some specialist orthopaedic oncology pathways, including our own, but this practice is not universal; many centres rely initially on clinical assessment and plain radiographs, with CT reserved for selected cases. We systematically reviewed the literature to compare evidence for Mirels, CTRA, and CT-based FEA in predicting pathologic femoral fractures. Methods A systematic search of MEDLINE and Embase was performed for studies published between 2005 and 2025. Eligible studies evaluated Mirels scoring, CTRA, or CT-based FEA in adult patients with femoral metastatic disease and reported subsequent pathologic femoral fracture outcomes. Two reviewers independently screened studies and extracted data. Potential cohort overlap was assessed by comparing authorship, recruiting institutions, enrolment periods, eligibility criteria, and descriptions of prior datasets. Management after fracture-risk assessment was examined to identify intervention-related bias. Due to heterogeneity in study design, imaging methods, and outcome reporting, a qualitative narrative synthesis was undertaken. Results Eight studies met the inclusion criteria, comprising prospective and retrospective clinical cohorts, an implementation study, and one illustrative comparative case series. In studies reporting formal diagnostic estimates, Mirels sensitivity ranged from 66.7% to 88%, while specificity ranged from 38% to 47.9%. In the principal prospective comparison, CTRA achieved 100% sensitivity and 60.6% specificity. Across formal FEA analyses, sensitivity ranged from 80% to 100% and specificity from 67% to 86%, although modelling methods, thresholds, and comparators varied. The evidence arose from small, partly overlapping cohorts, and prophylactic stabilization of lesions considered high risk limited observation of untreated outcomes and particularly the positive predictive value. Heterogeneity precluded meta-analysis. Conclusion Mirels remains a useful, accessible, and sensitive first-line screening tool, particularly where plain radiography is the principal imaging modality. CTRA and CT-based FEA may offer additional specificity and objective mechanical information in selected patients where suitable calibrated CT imaging and technical expertise are available, but current evidence does not support replacing clinical assessment and radiography. Whole-femur CT is routine in some specialist pathways, including our own, but not across all centres. Further progress will require prospective multicentre validation, standardized methodologies, health-economic assessment, and integration within multidisciplinary team pathways.
BACKGROUND:Platinum-etoposide combined with a PD-L1 inhibitor (atezolizumab or durvalumab) is the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). Although phase 3 trials have demonstrated similar efficacy, no direct comparison exists, and differences in treatment cost and resource utilization may influence clinical decision-making. METHODS:In this multicenter retrospective study, real-world data from eight Japanese institutions were analyzed. Patients with ES-SCLC treated with platinum-etoposide plus atezolizumab or durvalumab between August 2018 and December 2022 were included. Individual-level medical costs were calculated from health insurance claims linked to electronic medical records. After propensity score matching and exclusion of cisplatin-treated patients, 128 patients were analyzed. The primary outcome was mean monthly medical cost during immunotherapy. Secondary outcomes included overall survival (OS), immune-related adverse events (irAEs), and prognostic factors. RESULTS:Among 128 patients (mean age, 74 years; 85% male), mean monthly medical cost was significantly lower with atezolizumab than durvalumab (¥1 003 922 [$7183] vs ¥1 596 511 [$11 422]; P < .001). Median OS was comparable (13.9 months [95% CI, 11.7-17.5] vs 14.8 months [95% CI, 10.5-not reached]; P = .92). Grade ≥2 irAEs (11% vs 31%; P = .009) and interstitial lung disease (3% vs 20%; P = .004) were less frequent with atezolizumab. Poor performance status was associated with worse OS, whereas treatment type was not. CONCLUSIONS:Atezolizumab was associated with lower medical costs and similar survival outcomes compared with durvalumab in ES-SCLC, suggesting its use as a clinically comparable option with lower associated costs in Japanese real-world practice.
BACKGROUND:Severe postoperative complications (Clavien-Dindo [CD] grade ≥ 3) may compromise long-term oncologic outcomes after colorectal cancer (CRC) surgery, but their impact across all pathological stages remains unclear. METHODS:We retrospectively analyzed 1990 patients who underwent curative resection for pStage I-III CRC at six hospitals (2016-2021). Multivariable Cox proportional hazards models were used to evaluate recurrence-free survival (RFS), overall survival (OS), cancer-specific survival (CSS), and time to recurrence (TTR). Stratified analyses were performed by pathological stage and complication type (intra-abdominal infectious complications [IAI] vs. non-IAI), and a 30-day landmark analysis was conducted. RESULTS:CD ≥3 complications occurred in 128 patients (6.4%). On multivariable analysis, CD ≥3 complications were independent adverse prognostic factors for RFS (hazard ratio [HR] 1.84, P < .001), OS (HR 2.52, P < .001), and CSS (HR 2.04, P = .024), but not for TTR (HR 1.22, P = .451). Stage-stratified analyses showed significant associations with worse RFS and OS in pStage II-III, with trends in pStage I. CSS was significantly worse in pStage III (HR 3.06, P < .001). TTR showed no significant association with CD ≥3 complications in any pStage. IAI complications were independently associated with worse CSS (HR 2.21, P = .039), whereas non-IAI complications were not. These adverse effects persisted after 30-day landmark analysis. CONCLUSIONS:CD ≥3 complications independently worsen RFS, OS, and CSS but do not significantly affect TTR after curative resection for pStage I-III CRC. IAI complications are particularly associated with worse cancer-specific mortality. This discordance suggests that severe complications may not primarily accelerate recurrence itself, but may instead impair survival after recurrence, highlighting possible mechanisms beyond direct recurrence acceleration.
A 77-year-old male with monoclonal gammopathy of undertermined significance presented with multiple bulky extraosseous soft-tissue masses on imaging tests, mimicking radiological features of lymphoma. Ultimately, a diagnosis of multifocal extraosseous multiple myeloma was established, highlighting the need for comprehensive clinical and diagnostic correlation to ensure appropriate management.
Background:Reconstruction of diaphyseal bone defects of the lower limb after oncologic resection in children remains a major challenge. Several biological techniques are used, including the induced membrane technique (IMT), vascularized fibular graft (VFG), and combined allograft with vascularized fibula graft (CAVFG), but comparative data in pediatric populations remain limited. Questions/purposes:We asked: (1) What are the consolidation outcomes after biological reconstruction of pediatric lower-limb diaphyseal defects? (2) Which factors are associated with time to bone union? (3) What are the complication and revision profiles of these reconstruction strategies? Methods:We conducted a national multicenter retrospective study including pediatric patients (<18 years) who underwent diaphyseal resection of the femur or tibia for malignant bone tumors or adamantinoma between 2004 and 2024. Patients were reconstructed using IMT, VFG, or CAVFG. The primary endpoint was radiographic consolidation at 1 year. Secondary outcomes included overall union rate, time to union, complications, and revision surgery. Time-to-event analyses were performed using Kaplan-Meier and Cox regression models. Results:A total of 133 patients were included (IMT 69, VFG 22, CAVFG 42). Overall bone union was achieved in 72.9% of patients, with no significant difference between reconstruction techniques (IMT 75.4%, VFG 81.8%, CAVFG 64.3%; p = 0.272). Consolidation at 1 year, estimated by Kaplan-Meier analysis, occurred in 35.2% of cases. Median time to union was 18 months and did not differ significantly between techniques. Tibial localization was independently associated with higher union rates (OR 3.90, 95% CI 1.19-12.8; p = 0.024) and shorter time to union (HR 1.89, 95% CI 1.06-3.38; p = 0.032). Complications occurred in 64.1% of patients and 57% required revision surgery, without differences between techniques. Conclusion:Biological reconstruction of pediatric lower-limb diaphyseal defects allows limb salvage with acceptable union rates but prolonged healing and high complication rates. No technique demonstrated clear superiority, supporting an individualized reconstruction strategy based primarily on anatomical and mechanical considerations.
BACKGROUND:Transition from a palliative care unit (PCU) to home is clinically important in advanced cancer, but the sequence from planned or attempted transition through discharge realization and final place of death is insufficiently described. Electronic communication platforms may provide process markers of regional coordination. METHODS:We conducted a single-center prospective observational cohort study of consecutive patients with advanced cancer from 2018 to 2023. Patients were included when PCU-to-home transition was planned or attempted and they were registered in a regional electronic home palliative care communication platform derived from a paper-based pathway. We descriptively examined transition sequences, final place of death, non-home death subcategories, cumulative notebook count, and notebook entries per 7 home-care days. RESULTS:Among 209 planned or attempted transitions, 199 (95.2%) achieved actual home discharge and 10 (4.8%) remained unrealized. In the full cohort, home death occurred in 122 patients (58.4%) and non-home death in 87 (41.6%); 77 of 87 non-home deaths occurred in a PCU/palliative care unit. Among actual home-discharge patients, home death occurred in 122/199 (61.3%) and non-home death in 77/199 (38.7%). Median cumulative notebook counts were 23 [13-44] and 20 [10-40], respectively (descriptive P = 0.326). Median entries per 7 home-care days were 7.54 [2.62-19.76] and 5.13 [1.79-9.58] (descriptive P = 0.012). CONCLUSIONS:Most planned or attempted transitions achieved actual home discharge, but final place of death diverged thereafter. Notebook count and rate were descriptive communication-process markers that may help characterize and review multidisciplinary coordination across the ongoing regional transition process after PCU discharge.
BACKGROUND:The prognostic significance of non-muscle-invasive bladder cancer (NMIBC) recurrence after a prolonged disease-free interval following intravesical Bacillus Calmette-Guérin (BCG) therapy remains unclear. This multicenter study evaluated the impact of late recurrence after BCG therapy on oncological outcomes. METHODS:This retrospective multicenter study used the Japan Urological Oncology Group database. Among 3226 patients treated with intravesical BCG for NMIBC, 238 with non-muscle-invasive intravesical recurrence ≥1 year after initial BCG therapy were analyzed, after excluding those with muscle-invasive recurrence at first recurrence. Patients were stratified by time to recurrence: 1-2 years and ≥ 2 years. Progression-free survival (PFS) and cancer-specific survival (CSS) were assessed using Kaplan-Meier and Cox proportional hazards analyses. RESULTS:During a median follow-up of 72.7 months, the 5-year PFS and CSS rates were 90.8% and 91.5%, respectively. PFS did not differ significantly between the 1-2-year and ≥ 2-year recurrence groups (log-rank p = 0.300). In contrast, recurrence ≥2 years was associated with significantly worse CSS than recurrence at 1-2 years (log-rank P = .018) and was a significant predictor of worse CSS in univariate analysis (hazard ratio, 8.06; 95% confidence interval, 1.02-62.6; P = .047). Repeat BCG therapy did not significantly improve PFS or CSS in patients with recurrence ≥2 years. CONCLUSIONS:NMIBC recurrence occurring ≥2 years after initial BCG therapy may be associated with poorer cancer-specific survival despite similar progression-free survival. Late recurrence should not automatically be considered a favorable prognostic subgroup, and careful surveillance and risk stratification are warranted.
BACKGROUND:Radium-223 (Ra-223) is used for patients with bone-metastatic castration-resistant prostate cancer (CRPC). However, the prognostic value of regional lymph node metastasis at CRPC diagnosis for survival after Ra-223 remains unclear. This study evaluated the association between regional lymph node metastasis at CRPC diagnosis and overall survival (OS) after Ra-223 initiation. METHODS:This multicenter retrospective cohort study used the Following Ra-223 in Outcomes after New-generation Therapy with Investigation of Effects in Refractory prostate cancer study database. Patients with bone-metastatic CRPC who initiated Ra-223 between January 2020 and December 2023 were included. Patients were classified according to the presence or absence of regional lymph node metastasis at CRPC diagnosis. The primary endpoint was OS from Ra-223 initiation. Cox proportional hazards regression was used to evaluate the association between regional lymph node metastasis and OS. RESULTS:Among 802 patients who initiated Ra-223, 718 were included: 505 without regional lymph node metastasis and 213 with regional lymph node metastasis at CRPC diagnosis. Median OS was 31 months (95% confidence interval [CI], 26-35) and 17 months (95% CI, 16-22), respectively (log-rank P < 0.001). In multivariable analysis, regional lymph node metastasis at CRPC diagnosis was associated with poorer OS (hazard ratio, 1.396; 95% CI, 1.092-1.785; P = 0.008). CONCLUSIONS:Regional lymph node metastasis at CRPC diagnosis was associated with poorer OS after Ra-223 initiation. This status may provide prognostic information when considering subsequent treatment sequencing in bone-metastatic CRPC.
